Policy Issues in the Clinical Development and Use of Biomarkers for Molecularly Targeted Therapies: Device Issues

Transcription

1 Policy Issues in the Clinical Development and Use of Biomarkers for Molecularly Targeted Therapies: Device Issues Elizabeth Mansfield, PhD OIR/CDRH/FDA IOM April 1, 2015

2 Select Questions from the Committee Why are the current regulatory standards effective or ineffective for oversight of tests (including single biomarker tests and NGS tests) for molecularly-targeted therapies from your perspective? How do you see the regulatory environment changing over the next months, both expected and ideal? Are the levels of evidence requirements for companion diagnostics different than those for other IVD biomarker tests? Is regulatory oversight of tests for molecularly-targeted therapies coordinated between CDER and CDRH? Does FDA coordinate with CLIA/CMS (or other organizations with deemed status with CLIA) for regulatory oversight of tests, specifically of LDTs, so any new regulations do not conflict with current laboratory regulatory standards? Why is the regulatory oversight approach to next generation sequencing instruments, tests and bioinformatics taking a more open discussion process? Can this be generalized to other biomarker tests, like LDTs?

3 Quick Overview of IVD Regulation IVD products include reagents, instruments, and systems The usual way safe and effective is interpreted for IVDs is analytically and clinically valid Submissions include 510(k), PMA Investigational requirements apply to tests used in drug clinical trials

4 Why are the current regulatory standards effective or ineffective for oversight of tests (including single biomarker tests and NGS tests) for molecularly-targeted therapies from your perspective? Regulatory standard of safe and effective (analytical and clinical validity) applies to all medical devices Assures that Test is accurate and reliable for measurement/detection Test results have claimed clinical significance

5 How do you see the regulatory environment changing over the next months, both expected and ideal? 21CC legislation? Obviously, FDA could finalize LDT guidance NGS in the wings Oncology, germline/congenital disorders first FDA working toward cutting edge regulatory approach to NGS/WGS

6 Are the levels of evidence requirements for companion diagnostics different than those for other IVD biomarker tests? Same standard: safe and effective Analytically and clinically valid Analytical validation = same evidence requirements Clinical validation = leverage clinical trial outcomes Evidence requirements are specific to claims made for all tests*

7 Is regulatory oversight of tests for molecularly-targeted therapies coordinated between CDER and CDRH? Not really CDRH regulates tests CDER regulates drugs CDRH and CDER (and CBER) work together on every codevelopment project Internal meetings Timing Labeling

8 Does FDA coordinate with CLIA/CMS (or other organizations with deemed status with CLIA) for regulatory oversight of tests, specifically of LDTs, so any new regulations do not conflict with current laboratory regulatory standards? FDA has a long relationship (HHS, MOU) with CMS CLIA, categorization, parallel review, etc FDA, CLIA laws and regs for different purposes Do not conflict, are not duplicative FDA/CMS working together to help provide useful information and education to labs

9 Why is the regulatory oversight approach to next generation sequencing instruments, tests and bioinformatics taking a more open discussion process? Can this be generalized to other biomarker tests, like LDTs? Discussion processes can always be open Presub Propose guidance NGS/WGS has characteristics that are different from other IVDs Leverage characteristics for different oversight mechanisms Some project goals applicable to other technologies

10 Thanks